Table 4.

Enrichment of asthma risk loci in promoter and enhancer marks and DNase I-hypersensitive sites

Type of regulatory elements	Proportion of all cell types (blood cell types) showing enrichment with a given false discover rate (FDR)
	FDR ≤ 10%	FDR ≤ 5%
All promoter states	6% (26%)	0
Active promoter states	13% (33%)	0
All enhancer states	57%(100%)	44%(89%)
Active enhancer states	66% (100%)	50%(100%)
DNase I-hypersensitive sites	16% (50%)	12%(40%)

The co-localization of SNPs at asthma risk loci with regulatory elements (promoters, enhancers, DNase I-hypersensitive sites) was assessed at 16 asthma-loci identified by this study ( Table 1); the 6p21.33 and 6p21.32 loci that encompass the HLA region were excluded because of the high amount of variability and LD in this region. Enhancer and promoter states were defined using the ChromHMM 15-state model applied to functional data of 127 ROADMAP and ENCODE reference epigenomes in various cell types (including 27 leukocytes)²⁴. DNase I hypersensitivity sites were identified in 51 cell types (including 10 leukocytes)²⁴. Empirical-P-values for enrichment were obtained using 10,000 Monte-Carlo simulations of random sets of SNPs matching the original set of asthma-associated SNPs⁴⁰; Benjamini-Hochberg’s FDR was calculated to correct for multiple testing (Online Methods for details).